Our objective is to understand the mechanisms of action of lymphocyte mediators in several important reactions of cellular immunity. One of the mediators, migration inhibitory factor (MIF), inhibits the migration of macrophages out of capillary tubes against microbes and tumor cells. A closely related factor, macrophage activating factor (MAF) enhances the defense capacity of macrophages. Carbohydrates located on the macrophage membrane and associated with macrophage glycolipids are known to participate in the macrophage response to MIF and MAF. Macrophages preincubated with macrophage glycolipids exhibit an enhanced response to MIF, presumably through an increase of MIF receptors on the cell. Our investigations will examine the possible role of macrophage glycolipids as membrane receptors for MIF and MAF. Our plan of research will concentrate on the purification of the biologically active glycolipids to homogeneity and its subsequent structural analysis with respect to its composition, carbohydrate sequence, etc. Furthermore, the possible function of these macrophage glycolipids as receptors will be examined. We propose to investigate whether the pure active glycolipid can specifically and reversibly bind pH3-MIF and pH5-MIF. Assuming that the glycolipid can bind both MIF components and enhance the macrophage response to them, then we will ascertain which glycolipid carbohydrate residues are needed for these activities.